Mesoporous Inorganic Oxide Spheres and Method of Making Same

ABSTRACT

A method of preparing mesoporous inorganic oxide spherical particles includes providing a reaction mixture capable of producing mesoporous inorganic oxide spheres; heating the reaction mixture to produce mesostructured inorganic oxide particles and removing organic material from the mesostructured inorganic oxide particles to form the mesoporous inorganic oxide spherical particles. In one embodiment a reaction mixture includes a proton donor, a source of inorganic oxide, and a source of fluoride. In another embodiment a reaction mixture includes a proton donor, a source of inorganic oxide, and an alcohol. Mesoporous inorganic oxide spheres produced by the method of the present invention are also provided.

RELATED APPLICATION DATA

This application is a divisional of application Ser. No. 11/292,178,filed Dec. 1, 2005, entitled “Mesoporous Inorganic Oxide Spheres andMethod of Making Same,” which claims the benefit of U.S. ProvisionalPatent Application No. 60/632,830, filed Dec. 2, 2004, each of whichapplications are incorporated herein in their entireties.

FIELD OF THE INVENTION

The present invention generally relates to the field of inorganic oxideparticles. In particular, the present invention is directed to amesoporous inorganic oxide spherical particle and methods ofsynthesizing the same.

BACKGROUND OF THE INVENTION

Porous silica is commonly used as a matrix material for chromatographicseparations. With surface areas in the neighborhood of 300meter(m)²/gram(g), commercially available chromatographic grade silicaspossess a relatively high surface area. Mesoporous materials, whichtypically possess surface areas in excess of 1000 m²/g and even as highas 1600 m²/g, are commonly used as adsorbents, catalysts, and catalyticsupports. With such high surface areas, these materials should providesuperior separating ability as a chromatographic matrix in liquidchromatography (LC), flash liquid chromatography (FLC), and highperformance liquid chromatography (HPLC). Mesoporous inorganic oxideparticles differ from conventional porous inorganic oxides in that theirsurface areas are significantly larger than those of conventional porousinorganic oxides.

Various techniques exist for synthesizing mesoporous silica. Forexample, U.S. Pat. No. 4,554,211 to Arika et al., discloses a techniquefor synthesizing mesoporous silica spheres using an emulsion templatingmechanism in basic solution. Other patents describing techniques forsynthesizing large pore oxides in basic solution include U.S. Pat. Nos.5,068,216 to Johnson et al., 5,168,828 to Degnan et al., and 5,308,602to Calabro et al.

Recently, processes have been developed for synthesizing mesoporoussilica spheres in acidic solution. In an article by Stucky et al.,Oil-water Interface Templating of Mesoporous Macroscale Structures,Science, 1996, 273, 768-771 an emulsion process for synthesizingmesoporous silica spheres was described. A silicon alkoxide (TEOS) wasdissolved in an organic solvent, typically mesitylene. This mixture wasadded, slowly over a period of 30 minutes, to an aqueous acidic solutioncontaining a cationic ammonium surfactant (CTAB). Stucky found that byvarying the stir rate during the course of the reaction, the particlemorphology could be changed. At slower stirring rates, the reactionmixture produced fibers, and as the stirring rate was increased, theamount of fibers decreased with the increasing amounts of spheres. Itwas shown that the size of the spherical particles decreases withincreasing stirring rates. Scanning Electron Microscopy (SEM) indicatedthe particles were hollow and spherical in nature. It was shown thatthese hollow spheres were brittle, and could be crushed with a spatula.The brittle nature of the spheres, in combination with the fact thatthey were not porous throughout their interior, seemed to indicateunfavorable characteristics for their use a chromatographic matrix.

Qi et al., in the article Micrometer-Sized Mesoporous Silica SpheresGrown Under Static Conditions, Chemistry of Materials, 1998, 10,1623-1626, describes the formation of mesoporous silica spheres by aprocess using a cationic-nonionic surfactant mixture in aqueous acidicconditions. A typical synthesis involved stirring an aqueous acidicsolution of a cationic ammonium surfactant (CTAB), and a nonionicsurfactant (decaethylene glycol monohexadecylether), to which analkoxysilane was added (TEOS). This material was presumably porousthroughout its interior, although this was not specifically addressed inthe article. The material seems to possess desirable characteristics, ahigh surface area (1042 m²/g) and ˜5 micrometer (μm) particle size, foruse as a chromatographic matrix, but the long synthesis time (16 hours)and the use of a mixture of surfactants rather than one does not seemdesirable for use on a commercial scale.

Yet another process for synthesizing mesoporous silica spheres in acidicaqueous solution is described by Ozin et al., in the article Synthesisof Mesoporous Spheres Under Quiescent Aqueous Acidic Conditions, Journalof Materials Chemistry, 1998, 8(3), 743-750. An acidic aqueous solutionconsisting of an alkoxysilane (TEOS) and a cationic ammonium surfactant(CATCl), was allowed to react under static conditions for a period of7-10 days at 80° C. It was also demonstrated that spherical particlescould be synthesized at room temperature with a modified reactionmixture. Particle sizes appeared to range from 1-30 μm. While thespheres Ozin et al. produced are monodisperse, the lower surface area(750 m²/g) and long synthesis time (7-10 days) makes the material andprocess unattractive for use on a commercial scale. Monodispersityrefers to the degree to which the particles are uniform in size andshape, and must take into consideration the percentage of sphericalparticles, the size range of these particles, and their percentinterconnectivity.

All of the processes described above produce materials which exhibitregular powder X-ray diffraction patterns with one or more relativelynarrow diffraction peaks. This indicates that they contain a relativelyordered arrangement of pores. It appears that the materials produced bythese processes are similar to SBA-3, a mesoporous material with ahexagonal arrangement of linear pores (“Mesostructure Design with GeminiSurfactants: Supercage Formation in a Three-Dimensional Array”, Huo etal., Science, 1995, 268, 1324). SBA-3 is similar to the more widelyknown MCM-41, which has an identical arrangement of pores but issynthesized in basic solution (“Ordered Mesoporous Molecular SievesSynthesized by a Liquid-Crystal Templating Mechanism,” Kresge et al.,Nature, 1992, 359, 710). While mesoporous silica having such orderedpores has use in a variety of contexts, the processes for synthesizingsuch materials tends to take longer, or be more complex, than iscommercially desired.

Spherical Mesoporous silica particles have been produced using areaction mixture including fluoride. See “Spherical MSU-1 MesoporousSilica Particles Tuned for HPLC,” Boissiére, C.; Kummel, M.; Persin, M.;Larbot, A.; Prouzet, E. Adv. Funct. Mater. 2001, 11, 129-134. Suchparticles have relatively small pore volumes (0.45 cm³/g) and requirelong synthesis times (48-72 hours).

Spherical mesoporous silica particles have also been produced using areaction mixture including ethanol. See “Counterion Effect in AcidSynthesis of Mesoporous Silica Materials”, Lin, H.-P.; Kao, C.-P.; Mou,C.-Y.; Liu, S.-B. J. Phys. Chem. B. 2000, 104, 7885-7894. Such particlesare produced using a basic, as opposed to acidic, reaction mixturewithout the use of fluoride and require long synthesis times (6-48hours).

U.S. Pat. No. 6,334,988 to Gallis et al., the disclosure of which isincorporated herein in its entirety, discloses a method of makingmesoporous silicates from an acidic reaction mixture having a mineralacid, an inorganic oxide source, a surfactant, and water. However, thepore volume of the mesoporous silicates produced by such a method rangesfrom 0.35 cm³/g to 0.75 cm³/g. Further, the heating temperaturesrequired to achieve greater than 90% spherical particles range from 110°C. to 210° C. It is desirable to have mesoporous inorganic oxidespherical particles having larger pore volumes and larger pore diametersthan was previously achievable and methods of making such particles. Itis also desirable to be able to produce mesoporous inorganic oxidespherical particles with desirable properties in a shorter period oftime than in prior methods.

SUMMARY OF THE INVENTION

In one implementation, a mesoporous inorganic oxide spherical particleis provided. The mesoporous inorganic oxide spherical particle in thisimplementation is produced by a method that includes providing areaction mixture including: a proton donor; a source of inorganic oxide;and a source of fluoride; heating said reaction mixture for not morethan 120 minutes to produce mesostructured inorganic oxide particles;and removing organic material from said mesostructured inorganic oxideparticles to form the mesoporous inorganic oxide spherical particles.

In another implementation, a plurality of mesoporous inorganic oxidespherical particles are provided. The plurality of mesoporous inorganicoxide spherical particles in this implementation each include one ormore pores, have a pore volume of greater than 0.75 cm³/g, and have anaverage pore diameter of greater than 37 Angstroms.

BRIEF DESCRIPTION OF THE DRAWINGS

For the purpose of illustrating the invention, the drawings show a formof the invention that is presently preferred. However, it should beunderstood that the present invention is not limited to the precisearrangements and instrumentalities shown in the drawings, wherein:

FIG. 1 shows a plot of a powder X-ray diffraction (“XRD”) analysis forone example of mesoporous inorganic oxide spheres according to thepresent invention;

FIG. 2 shows a plot of a gas/adsorption/desorption isotherm for oneexample of mesoporous inorganic oxide spheres according to the presentinvention;

FIG. 3 shows a plot of pore diameter for one example of mesoporousinorganic oxide spheres according to the present invention;

FIG. 4 shows a plot of chromatographs for each of three stationaryphases, including a stationary phase comprising mesoporous inorganicoxide spheres according to the present invention; and

FIGS. 5 to 11 show various data for a plurality of examples ofmesoporous inorganic oxide spheres produced according to examples of themethod of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present disclosure includes improved methods of synthesizingmesoporous inorganic oxide particles, particularly silicate particles.The synthesis occurs using an acidic aqueous reaction procedure over ashorter period of time than other synthesis for similar particles.Mesoporous inorganic oxide particles differ from conventional porousinorganic oxides in that their surface areas are significantly largerthan those of conventional porous inorganic oxides. For example, thesurface area of the mesoporous inorganic oxide particles of the presentinvention are in excess of about 800 m²/g and, in some cases, in excessof 1200 m²/g. In comparison, well known inorganic oxide, conventionalchromatographic grade silicas, generally have a surface area less than500 m²/g, and commonly less than 300 m²/g.

The methods of the present invention provide mesoporous inorganic oxideparticles that are spherical and have a greater pore volume than knownmesoporous inorganic oxide particles.

A particle is considered spherical if it displays a spheroidal shape,whether free standing or attached to other particles. The sphericalquality of a particle is measured using scanning electron microscopy(SEM). A spherical particle provides greater functionality than anon-spherical particle. Spherical particles pack together, for examplein a chromatography column, such that there is always some empty spacebetween them. In chromatography it is essential that some space existbetween the column particles such that the sample molecules can flowaround the column particles. Spherical particles also have the advantageof being more readily recognized by microscopic techniques, such asfluorescence microscopy and electron microscopy, which have difficultydistinguishing non-spherical particles from one another.

The temperature required during synthesis over the shorter periods oftime to achieve a high percentage of spherical particles is lower thanthat of known processes. A lower temperature, preferably a temperaturebelow the boiling point of water (100° C.), provides for more efficientand affordable scaling of the synthesis to commercial scales. Themethods of the present invention utilize a heating step that heats thereaction mixture at a temperature of about 50° C. to about 230° C. Inone example of the present invention, greater than 95% sphericalparticles are produced at a temperature of about 70° C. In anotherexample of the present invention, greater than 90% spherical particlesare produced at a temperature of about 25° C. (room temperature, “RT”).

In one embodiment of the present invention, a method of preparing amesoporous inorganic oxide spherical particle is provided. The methodincludes providing a reaction mixture having a source of inorganic oxideand being capable of forming a mesoporous inorganic oxide sphere. Thereaction mixture is heated for a selected time and organic material isremoved from the resulting product to form a mesoporous inorganic oxidespherical particle having a desirably large pore volume.

A reaction mixture according to the present invention may also includeother constituents. Other constituents may include, but are not limitedto, a source of fluoride, an alcohol, a proton donor, a surfactant, andwater. The reaction mixture may also include a metal salt. Theconstituents of a reaction mixture may be mixed (e.g., by stirring) fora selected time prior to the mixture being heated.

In one embodiment of the present invention, a source of inorganic oxidemay include any material that is a source of silicate. In one aspect, asource of silicate can include a compound having a formulaSi(OR¹)(OR²)(OR³)(OR⁴) where Si is silicon, O is oxygen, and R¹, R², R³,and R⁴ are alkyl chains having 1 to 4 carbon atoms. Examples of sourcesof silicate include, but are not limited to, tetraethoxysilane,tetramethoxysilane, tetrapropoxysilane, and any combinations thereof. Inone embodiment of the present invention, the source of inorganic oxideis tetraethoxysilane (also known as tetraethyl orthosilicate or TEOS)sold by Sigma-Aldrich.

In one example, an inorganic oxide may be present in the reactionmixture of the present invention in an amount from about 0.017 mole(mol) % to about 1.6 mol %. In another example, an inorganic oxide maybe present in the reaction mixture of the present invention in an amountfrom about 0.3 mol % to about 1.2 mol %. In yet another example, aninorganic oxide may be present in the reaction mixture of the presentinvention in an amount from about 0.6 mol % to about 0.8 mol %. In stillanother example, an inorganic oxide may be present in the reactionmixture of the present invention in an amount of about 0.6 mol %.

In one embodiment of the present invention, the source of fluoride is asalt that includes a fluoride ion. Examples of suitable sources offluoride include, but are not limited to, sodium fluoride, potassiumfluoride, ammonium fluoride, other fluoride salts, and any combinationsthereof. In one embodiment of the present invention, the source offluoride is a 0.5 Molar (M) solution of sodium fluoride prepared fromsodium fluoride sold by Sigma-Aldrich.

In one example, a source of fluoride is present in the reaction mixtureof the present invention in an amount from about 0.019 mol % to about0.2 mol %. In another example, a source of fluoride is present in thereaction mixture of the present invention in an amount from about 0.039mol % to about 0.17 mol %. In yet another example, a source of fluorideis present in the reaction mixture of the present invention in an amountfrom about 0.072 mol % to about 0.1 mol %. In still another example, asource of fluoride may be present in the reaction mixture of the presentinvention in an amount of about 0.08 mol %.

In one embodiment of the present invention, an alcohol is awater-miscible alcohol. Examples of water-miscible alcohols include, butare not limited to, ethanol, methanol, n-propanol, isopropanol, and anycombinations thereof. In one example, an alcohol includes 200 proofethanol sold by AAPER Alcohol and Chemical Co.

In one example, an alcohol is present in the reaction mixture of thepresent invention in an amount from about 1.9 mol % to about 20 mol %.In another example, an alcohol is present in the reaction mixture of thepresent invention in an amount from about 2.9 mol % to about 15.4 mol %.In yet another example, an alcohol is present in the reaction mixture ofthe present invention in an amount from about 3.9 mol % to about 13.5mol %. In still another example, an alcohol may be present in thereaction mixture of the present invention in an amount of about 4 mol %.

In one embodiment of the present invention, a proton donor includes anacid. Examples of acids suitable for use as a proton donor include, butare not limited to, HCl, HBr, HI, HNO₃, H₂SO₄. In one example, a protondonor includes a concentrated (37.2 wt. %) solution of hydrochloric acidsold by Fischer Scientific.

In one example, a proton donor is present in the reaction mixture of thepresent invention in an amount from about 0.3 mol % to about 3.4 mol %.In another example, a proton donor is present in the reaction mixture ofthe present invention in an amount from about 0.9 mol % to about 2.7 mol%. In yet another example, a proton donor is present in the reactionmixture of the present invention in an amount from about 1.39 mol % toabout 1.76 mol %. In still another example, a proton donor is present inthe reaction mixture of the present invention in an amount of about 1.5mol %.

In one embodiment of the present invention, a surfactant includes acationic surfactant. In another embodiment of the present invention, asurfactant includes a cationic ammonium having a formula R¹R²R³R⁴N⁺X⁻,where R¹, R² and R³ are alkyl chains consisting of 1 to 6 carbon atoms,R⁴ is an alkyl chain consisting of 12 to 24 carbon atoms and X⁻represents a counterion to said surfactant, said counterion selectedfrom the group consisting of Cl⁻, Br⁻, I⁻ and OH⁻. In yet anotherembodiment of the present invention, a surfactant includes a tri-blockcopolymer EO_(x)PO_(y)EO_(x), where EO is polyethylene oxide, PO ispolypropylene oxide and x ranges from 5 to 106, y ranges from 30 to 85and z ranges from 5 to 106. In still yet another embodiment of thepresent invention, a surfactant includes a salt having atrialkylammonium cation and a halide anion. In a further embodiment ofthe present invention, multiple surfactants can be used. Using multiplesurfactants is commercially advantageous in that various pore diametersand physical properties are introduced into the material in a singleprocess.

Examples of suitable surfactants include, but are not limited to,cetyltrimethylammonium bromide, cetyltrimethylammonium chloride,tetradecyltrimethylammonium bromide, lauryltrimethylammonium bromide,lauryltrimethylammonium chloride, tetradecyltrimethylammonium chloride,poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethyleneglycol), and any combinations thereof. In one example, a surfactantincludes cetyltrimethylammonium bromide (CTAB) sold by Sigma-Aldrich.

In one example, a surfactant is present in the reaction mixture of thepresent invention in an amount from about 0.01 mol % to about the limitof solubility. In another example, a surfactant is present in thereaction mixture of the present invention in an amount from about 0.119mol % to about 0.26 mol %. In yet another example, a surfactant ispresent in the reaction mixture of the present invention in an amount ofabout 0.16 mol %.

Table 1 summarizes several example approximate mol % ranges for variousconstituents that may be present in a reaction mixture according to thepresent invention.

TABLE 1 Example reaction mixture constituent ranges Reaction MixtureExample approximated ranges of mole % Constituent (mol %) in reactionmixture Inorganic Oxide 0.0174 mol %-1.63 mol %  0.318 mol %-1.20 mol % 0.618 mol %-0.760 mol % Fluoride 0.0190 mol %-0.192 mol %  0.0390 mol%-0.167 mol %  0.0720 mol %-0.0990 mol % Alcohol 1.92 mol %-19.4 mol %2.94 mol %-15.4 mol % 3.96 mol %-13.5 mol % Proton Donor 0.366 mol%-3.35 mol %  0.910 mol %-2.68 mol %  1.39 mol %-1.76 mol % Surfactant0.01 mol %-limit of solubility 0.115 mol %-0.253 mol %

One embodiment of a reaction mixture according to the present inventionmay include an inorganic oxide, a source of fluoride, an alcohol, aproton donor, a surfactant, and water. In one example, a reactionmixture according to this embodiment may include TEOS, sodium fluoride,ethanol, hydrochloric acid, CTAB and water. In another example, areaction mixture according to this embodiment may include about 0.6 mol% TEOS, about 0.08 mol % sodium fluoride, about 4 mol % ethanol, about1.5 mol % HCl, about 0.16 mol % CTAB, and about 91.2 mol % water.

In one embodiment of the present invention, the constituents of areaction mixture are combined and mixed until chemically homogenous. Inone example, this combination and mixing can be done at roomtemperature. In another example, the mixing can be done at a temperatureof about 25° C. to about 35° C. The mixing may be accomplished bystirring, by sonication involving use of a sonication horn of the typesold by Heat Systems-Ultrasonics, Inc. of Farmingdale, N.Y. (one modelof sonication horn operating at a frequency and maximum power,respectively, of 20,000 kHz and 475 watts), or by any other technique ortechniques yielding a chemically homogenous mixture. After the additionof all reaction mixture constituents, the mixing is continued until thereaction mixture is sufficiently polymerized such that a mesostructuredinorganic oxide sphere may be formed upon heating the reaction mixtureas discussed in greater detail below. In one example, sufficientpolymerization is indicated by the reaction mixture turning opaque. Asused in this context and in the claims, an “opaque” mixture means amixture having a transparent to white color and containing a suspensionof very small particles that cannot be captured by Buchner filtration onVWR qualitative filter paper grade 413. Typical times for mixing includeabout 15 seconds to about 2.5 hours, depending on the composition of thereaction mixture. In another example, the time of mixing is about 25sec. to about 360 sec. While it is typically advantageous to achievechemical homogeneity as quickly as possible, in some cases it may bedesirable to extend the mixing period. This can be achieved by reducingeither the acid and/or fluoride concentrations and/or increasing theethanol concentration in the reaction mixture.

The reaction mixture is then heated at a temperature, time, and pressuresufficient to form one or more mesostructured inorganic oxide spheres. Amesostructured inorganic oxide sphere includes inorganic material, forexample inorganic oxide, and organic material, for example surfactant,intimately combined as a composite particle. The heating step can takeplace in any vessel capable of withstanding the selected temperature,time, and pressure. One example of a vessel suitable for the heatingstep is a Teflon bottle. Another example of a vessel suitable for theheating step is a stainless steel autoclave, such as model 4748 andmodel 4749 t-lined stainless steel autoclaves sold by Parr InstrumentsCo. of Moline, Ill.

The reaction mixture is heated during this step at a temperaturesufficient to produce the mesostructured inorganic oxide sphere. In oneexample, the reaction mixture is heated at a temperature from about 50°C. to about 230° C. In another example, the reaction mixture is heatedat a temperature from about 70° C. to about 200° C. In yet anotherexample, the reaction mixture is heated at a temperature from about 90°C. to about 150° C. In still another example, the reaction mixture isheated at a temperature below about 100° C. In still yet anotherexample, the reaction mixture is heated at a temperature of about 70° C.

The heating step occurs for a period of time sufficient to produce themesostructured inorganic oxide sphere at the selected temperature. Lowertemperatures typically require longer time for the same reaction mixturecomponents. In one example, the reaction mixture is heated for not morethan 120 minutes. In another example, the reaction mixture may be heatedfor a time that may range from about 10 minutes to about 80 minutes. Inyet another example, the reaction mixture may be heated for a time thatmay range from about 20 minutes to about 60 minutes. In still anotherexample, the reaction mixture may be heated for about 40 minutes.

The resulting mesostructured inorganic oxide sphere can be separatedfrom any remaining reaction mixture by a conventional technique, such asfiltration. The filtered mesostructured inorganic oxide sphere can bedried using a conventional technique, such as vacuum filtration. Thefiltration and drying steps may be combined or separate steps. In oneexample, the drying of a mesostructured inorganic oxide sphere isperformed at about room temperature. In another example the drying canoccur at any temperature as long as it is not high enough to causedecomposition of the surfactant.

Organic material, such as surfactant, is removed from a mesostructuredinorganic oxide sphere to produce a mesoporous inorganic oxide sphere.Examples of suitable techniques for removing the organic materialinclude, but are not limited to, burn away of the organic material awaywith such a technique as calcining, wash-out of the organic material,ion exchange, and any combination thereof. In one example, the organicmaterial is removed by heating the material to a temperature in therange of about 400° C. to about 600° C. with a temperature ramp of about0.2° C./minute to about 5° C./minute, preferably no more than 2°C./minute, and then maintaining the material at such temperature for atleast about 6 hours. In another example, the organic material is removedin a two-step process where the mesostructured inorganic oxide sphere isheated at a temperature ramp of about 2° C./minute to a temperature ofabout 450° C., where it is maintained for about 4 hours. Then, thetemperature is elevated at a temperature ramp of about 10° C./minute to550° C., where it is maintained for about 8 hours. In yet anotherexample, the organic material is removed by ion exchange using diluteHCl dissolved in ethanol.

Unlike particles that are a thin silica shell formed around a singlelarge void (often formed by polymerizing a spherical silica shell aroundan oil droplet), such as those described by Schacht et al., a mesoporousinorganic oxide sphere produced by a method of the present invention isnot hollow, but has a mesoporous region that continues throughout theinterior of the particle.

Powder X-ray diffraction (“XRD”) analysis of mesoporous inorganic oxidespheres of the present invention showed either one unusually broad peakwith very low intensity or no diffraction at all, indicating adisordered product. In one example, XRD analysis provided the plot inFIG. 1. The plot in FIG. 1 shows an XRD pattern n the region between 1and 8 degrees 2 θ for a sample of mesoporous inorganic oxide spheresproduced according to the present invention. XRD analysis was performedon a Scintag X1 θ-θ diffractometer equipped with a Peltier (solid-statethermoelectrically cooled) detector using Cu Kα radiation. X-rayradiation with a wavelength of 1.5456 Angstroms was emitted from a Cutarget and fired at the sample. According to the Bragg equation(nλ=2dsinθ), coherent diffraction from regions of ordering in the samplewith a repeat distance of d will occur at an angle θ. Thus, theobservation of multiple peaks with narrow peak widths would be anindication of an ordered sample, and the locations within the sample ofthe regions creating the ordering could be estimated from the positionsof the peaks. The presence of a single, very broad peak in the patternof FIG. 1 indicates that although the sample may have some weakordering, in general it is disordered. The pores within the sample haverandom locations relative to each other. Disordered product is mostlikely due to the S⁺X⁺I⁺ method of self-assembly that occurs in acidicsolution, in which interactions between a cationic surfactant andcationic silicate species are mediated by an anionic counterion. Theinteractions between the surfactant and silicate are therefore muchweaker than in basic solution, where the silicate is anionic andinteracts directly with the surfactant through electrostatic attraction(S⁺I⁻).

Mesoporous inorganic oxide spheres produced in accordance with thepresent invention have a high concentration of spherical particles and aremarkably narrow particle size distribution. Table 2 sets forth data ofthe high degree of spherical particles produced at various temperaturesusing a method of the present invention versus the degree of sphericalparticles produced at the same temperatures using a known method (amethod set forth in U.S. Pat. No. 6,334,988 to Gallis et al.). In oneexample, at least about 90% of the particles produced in accordance witha method of the present invention were spherical. In another example, atleast about 95% of the particles produced in accordance with a method ofthe present invention were spherical.

TABLE 2 Examples of Mesoporous inorganic Temper- oxide spheres producedin accordance Particles of U.S. ature with the present invention Pat.No. 6,334,988 ° C. % Spheres % interconnected % Spheres 25 ~90 (0.5-1.5um) 50 <50 50 >90 (0.5-2 um) 25 ~50 70 >95 (1-2.5 um) 15 >60 90 >95(1.5-3 um) 10 >80 100 >95 (1.5-3 um) 10 >90 150 >95 (1-3 um) <10 >90

Mesoporous inorganic oxide spheres produced in accordance with thepresent invention have a particle diameter that is advantageously small.In one example, the diameter of mesoporous inorganic oxide spheresproduced by a method of the present invention range from about 0.1 μm toabout 8 μm. In another example, the diameter of mesoporous inorganicoxide spheres produced by a method of the present invention range fromabout 1 μm to about 3 μm.

A mesoporous inorganic oxide sphere produced in accordance with thepresent invention has large surface area. Larger surface area isparticularly important in applications such as chromatography where thelarger the surface area, the greater the enhancement of resolutionbetween peaks. In one example, mesoporous inorganic oxide spheresproduced in accordance with the present invention have a surface areafrom about 400 m²/g to about 1200 m²/g. In another example, mesoporousinorganic oxide spheres produced in accordance with the presentinvention have a surface area from about 800 m²/g to about 1000 m²/g.Surface areas of mesoporous inorganic oxide spheres produced inaccordance with the present invention were measured using the BETtechnique described in the article by S. Brunauer et al. in the Journalof the American Chemical Society, 1938, volume 60, page 309, which isincorporated herein by reference in its entirety. N₂ adsorption anddesorption isotherms were obtained on a Micromeritics ASAP 2010instrument. Samples were degassed at 200° C. under vacuum overnightprior to measurement.

In one example, a sample of mesoporous inorganic oxide spheres producedin accordance with the present invention were placed in a high vacuumand nitrogen (N₂) was incrementally added to the sample chamber. Asensitive pressure transducer measured the volume relative to a standardheld at a constant pressure, to account for environmental variationsduring the course of the experiment. FIG. 2 below shows agas/adsorption/desorption isotherm for this example. The total surfaceof the area of the sample was calculated from this isotherm using theBET technique.

Mesoporous inorganic oxide spheres produced in accordance with thepresent invention have larger pore volumes than other known mesoporousinorganic oxide spheres. Larger pore volume is important becauseparticles with large pore volumes have a higher permeability and ahigher loading capacity than those with small pore volumes. For example,in size exclusion chromatography, it is desirable to use a columnmaterial with a large pore volume because the elution volume of theretained molecules, and therefore the separation between them, isincreased. A chromatography column containing a material with a largepore volume has a large separating power. In one example, mesoporousinorganic oxide spheres produced in accordance with the presentinvention have a pore volume greater than about 0.65 cm³/g. In anotherexample, mesoporous inorganic oxide spheres produced in accordance withthe present invention have a pore volume greater than about 0.75 cm³/g.In yet another example, mesoporous inorganic oxide spheres produced inaccordance with the present invention have a pore volume greater thanabout 0.85 cm³/g.

In one embodiment, the mesoporous inorganic oxide spheres produced by amethod of the present invention include a mesoporous spherical body. Themesoporous spherical body includes a plurality of pores. In one example,the plurality of pores has a pore volume greater than about 0.65 cm³/g.In another example, the plurality of pores has a pore volume greaterthan about 0.75 cm³/g. In yet another example, the plurality of poreshas a pore volume greater than about 0.85 cm³/g. In still anotherexample, mesoporous inorganic oxide spheres produced in accordance withthe present invention have a pore volume greater than 0.75 cm³/g and anaverage pore diameter of greater than 37 Angstroms. In still yet anotherexample, mesoporous inorganic oxide spheres produced in accordance withthe present invention have a pore volume greater than about 1 cm³/g andan average pore diameter of greater than about 50 Angstroms. In afurther example, mesoporous inorganic oxide spheres produced inaccordance with the present invention have a pore volume of greater thanabout 1.3 cm³/g.

In one example, using the gas adsorption/desorption isotherm from FIG.2, the plot in FIG. 3 was produced. A series of pore diameter ranges wasestablished from the isotherm and the portion of the N₂ absorbed due tothe pores in each range was determined. A tabulation of pore volumesversus the average pore diameter in each range was created. A largeadsorption at a particular average pore diameter implies that there mustbe a large number of pores with that diameter in the sample. The totalpore volume and pore size distribution can be calculated from the plotin FIG. 3 using the method described by Barrett, Joyner, and Halenda (J.Am. Chem. Soc. 1951, 73, 373), which is incorporated herein by referencein its entirety. However, the data shown in FIG. 3 was calculated usingan updated method that more accurately accounts for adsorption insidepores with diameters between 20 and 40 Angstroms. Such a method is setforth in an article by Kruk, M.; Jaroniec, M.; Sayari, A. in Langmuir1997, 13, 6267, which is incorporated herein by reference in itsentirety.

Mesoporous inorganic oxide spheres produced in accordance with thepresent invention can be used as the stationary phase in chromatographicseparations. Examples of chromatographic techniques in which themesoporous inorganic oxide spheres of the present invention are highlyeffective include, but are not limited to, conventional liquidchromatography (“LC”), normal phase flash liquid chromatography (FLC),high pressure liquid chromatography (“HPLC”), reverse phase FLC, andreverse phase HPLC. Use of pressure in FLC and HPLC alleviates theproblem of backpressure often associated with the use of small particlesin chromatography.

HPLC (high performance liquid chromatography) is a technique in which asolid material, usually silica, is packed into a stainless steel column.A liquid containing a mixture of dissolved chemicals that are to beseparated is then pushed through the column under pressure. Thechemicals have different levels of adsorption onto the silica, and sothey travel through the column at different rates; chemicals that adsorbstrongly to silica travel slowly, and those that adsorb weakly travelrapidly. This effectively separates one chemical from another. The typeof liquid clearly also has an effect, since chemicals that are not verysoluble in the liquid will also tend to travel slowly through the HPLCcolumn. In a normal-phase HPLC separation, the silica is unmodified andis hydrophilic, and a hydrophobic liquid such as hexane is used. Peaksarise as a result of spectroscopic detection as they emerge from thecolumn. The test separation shown above is frequently used to gauge theeffectiveness of types of silica in HPLC.

To demonstrate the viability of mesoporous inorganic oxide spheresproduced in accordance with the present invention for use as astationary phase in chromatography, three HPLC stationary phases werecompared for use in separation of benzene, naphthalene, and biphenyl.The three stationary phases used were 1) mesoporous inorganic oxidespheres produced in accordance with the present invention (“APMS2”), 2)inorganic oxide particles produced according to U.S. Pat. No. 6,334,988(“APMS”), and 3) Nucleosil (a commercially available silica purchasedfrom Phenomenex (advertised particle size 5 μm and pore size 50 Å). Wehave SEMs and our own porosity data for this Nucleosil material (surfacearea 369 m²/g, pore volume 0.837 cm³/g, Average pore diameter 116 Å,particle size 4-6 μm)).

HPLC separations were performed for the three different stationaryphases using a Hewlett Packard series 1100 HPLC operating with a flowrate of 1 mL/min and an injection volume of 5 μL. A UV detectoroperating a 254 nm was used in the detection of all compounds. Stainlesssteel HPLC columns (50×4.6 mm, Phenomenex) were used for theseseparations. All materials were slurry packed (0.5-1 g of silica) intothese columns with a 98.3% hexane and 1.7% dichloromethane solutionunder 5200 psi. Individual column conditions for the separations mobilephase 98.3:1.7 (Hexane:dichloromethane) for all of the columns, columntemperature 30° C. for all of the columns, and Pressure for APMS 7 bar,APMS2 11 bar, and Nucleosil 10 bar.

FIG. 4 shows the resulting chromatographs for each of the threestationary phases. Table 3 shows information taken from each of thechromatographs.

TABLE 3 peak APMS APMS2 Nucleosil benzene (1) t_(R1) (minutes) 2.13 1.471.38 w_(1/2) (minutes) 0.139 0.0927 0.0854 k′₁ 1.82 0.863 0.756 N 12901400 1460 naphthalene (2) t_(R1) (minutes) 3.59 2.02 1.90 w_(1/2)(minutes) 0.175 0.967 0.959 k′₁ 3.77 1.56 1.41 N 2330 2420 2170 biphenyl(3) t_(R1) (minutes) 5.86 2.68 2.65 w_(1/2) (minutes) 0.276 0.124 0.122k′₁ 10.3 4.28 4.27 N 2500 2610 2630 α₁₋₂ 2.06 1.80 1.86 α₁₋₃ 5.65 4.965.65 α₂₋₃ 2.74 2.75 3.03

The retention time is indicated by t_(R); w_(1/2) is the width of thepeak at half of its intensity; k′ is the capacity factor of the columnfor the analyte, and N is the number of theoretical plates of the columnwhen separating the compound (a measure of the separating ability of thecolumn; larger N leads to greater separating effectiveness). α is aratio of k′ for one compound to k′ for another. Ideally, one wouldobserve narrow (small w_(1/2)), well separated peaks (large values ofα), that elute as quickly as possible (small values of t_(R)), withlarge values of N. The above data shows that although APMS is prettygood at separating one compound from another, it can produce broad peakswith long retention times. APMS2, on the other hand, shows separationproperties that are much closer to commercially used materials and are adistinct improvement over APMS.

In one embodiment of the present invention, a method of performing aliquid chromatographic separation of a liquid or dissolved solidcompound is provided. The method includes packing a chromatographycolumn with a slurry having a plurality of mesoporous inorganic oxidespherical particles made in accordance with the present invention. Theslurry includes an organic solvent selected as a function of said liquidor dissolved solid compound to be separated. The method also includesadding the liquid or dissolved solid compound to the slurry; andretrieving a mobile phase of the liquid or dissolved solid compound fromthe chromatography column. The chromatography column can be a highpressure liquid chromatography column. In one example, the separationcan include binding of an alkylsilane onto a mesoporous inorganic oxidespherical particle. by binding a chiral molecule onto said mesoporousinorganic oxide spherical particle. In another example, the separationcan include adding a chiral molecule into said mobile phase during saidseparation.

FIGS. 5 to 11 show various data for multiple examples of mesoporousinorganic oxide spheres produced in accordance with the presentinvention. For each example, the mol % of each reaction mixtureconstituent is presented. Additionally, the time for visual indicationof precipitation of spheres is given in seconds (sec.) for each example.The surface area in meters squared per gram (m²/g), pore volume in cubiccentimeters per gram (cc/g), pore diameter in Angstroms (Å), particlesize in micrometers (μm), % of particles that are spherical, and %interconnection of particles are given for each example. The temperatureand time of the mixing of the reaction mixture is indicated (the mixingwas done at room temperature, “RT”). The temperature of heating is givenin degrees Celsius (° C.) and the time of heating is indicated inminutes (min.).

FIG. 5 illustrates six examples with varying amounts of TEOS in areaction mixture. FIG. 6 illustrates five examples with varying amountsof sodium fluoride in a reaction mixture. FIG. 7 illustrates sevenexamples with varying amounts of HCl in a reaction mixture. FIG. 8illustrates six examples with varying amounts of ethanol in a reactionmixture. FIG. 9 illustrates five examples with varying amounts of CTABin a reaction mixture. FIG. 10 illustrates six examples with variedheating temperatures. FIG. 11 illustrates six examples with varied timeof heating.

Although the invention has been described and illustrated with respectto exemplary embodiments thereof, it should be understood by thoseskilled in the art that the foregoing and various other changes,omissions and additions may be made therein and thereto, without partingfrom the spirit and scope of the present invention.

1. A mesoporous inorganic oxide spherical particle produced by a methodcomprising: providing a reaction mixture including: a proton donor; asource of inorganic oxide; and a source of fluoride; heating saidreaction mixture for not more than 120 minutes to produce mesostructuredinorganic oxide particles; and removing organic material from saidmesostructured inorganic oxide particles to form the mesoporousinorganic oxide spherical particles.
 2. A method according to claim 1,further comprising: mixing said reaction mixture sufficiently prior tosaid heating step so that said mesostructured inorganic oxide sphere maybe formed as a result of said heating step.
 3. A mesoporous inorganicoxide spherical particle according to claim 2, wherein said mixing stepis performed until said reaction mixture is opaque.
 4. A mesoporousinorganic oxide spherical particle according to claim 1, wherein saidreaction mixture further includes: an alcohol; a surfactant; and water.5. A mesoporous inorganic oxide spherical particle according to claim 1,wherein said proton donor is present in an amount from about 0.3 mol %to about 3.4 mol %.
 6. A mesoporous inorganic oxide spherical particleaccording to claim 1, wherein said proton donor is present in an amountof about 1.5 mol %.
 7. A mesoporous inorganic oxide spherical particleaccording to claim 1, wherein said proton donor comprises hydrochloricacid.
 8. A mesoporous inorganic oxide spherical particle according toclaim 1, wherein said source of inorganic oxide comprises a compoundhaving a formula Si(OR¹)(OR²)(OR³)(OR⁴) where Si is silicon, O isoxygen, and R¹, R², R³, and R⁴ are alkyl chains having 1 to 4 carbonatoms.
 9. A mesoporous inorganic oxide spherical particle according toclaim 1, wherein said source of inorganic oxide comprisestetraethoxysilane.
 10. A mesoporous inorganic oxide spherical particleaccording to claim 1, wherein said source of inorganic oxide is presentin an amount from about 0.017 mol % to about 1.6 mol %.
 11. A mesoporousinorganic oxide spherical particle according to claim 1, wherein saidsource of inorganic oxide is present in an amount of about 0.6 mol %.12. A mesoporous inorganic oxide spherical particle according to claim1, wherein said source of fluoride is present in an amount from about0.019 mol % to about 0.2 mol %.
 13. A mesoporous inorganic oxidespherical particle according to claim 1, wherein said source of fluorideis present in an amount of about 0.08 mol %.
 14. A mesoporous inorganicoxide spherical particle according to claim 1, wherein said source offluoride comprises sodium fluoride.
 15. A mesoporous inorganic oxidespherical particle according to claim 1, wherein said reaction mixturefurther comprises an alcohol.
 16. A mesoporous inorganic oxide sphericalparticle according to claim 15, wherein said alcohol is present in anamount from about 1.9 mol % to about 20 mol %.
 17. A mesoporousinorganic oxide spherical particle according to claim 15, wherein saidalcohol is present in an amount of about 4 mol %.
 18. A mesoporousinorganic oxide spherical particle according to claim 15, wherein saidalcohol comprises ethanol.
 19. A mesoporous inorganic oxide sphericalparticle according to claim 1, wherein said reaction mixture furthercomprises a surfactant.
 20. A mesoporous inorganic oxide sphericalparticle according to claim 19, wherein said surfactant is present in anamount from about 0.01 mol % to about the limit of solubility.
 21. Amesoporous inorganic oxide spherical particle according to claim 19,wherein said surfactant is present in an amount of about 0.06 mol %. 22.A mesoporous inorganic oxide spherical particle according to claim 19,wherein said surfactant comprises a salt having a trialkylammoniumcation and a halide anion.
 23. A mesoporous inorganic oxide sphericalparticle according to claim 19, wherein said surfactant comprisescetyltrimethylammonium bromide.
 24. A mesoporous inorganic oxidespherical particle according to claim 1, wherein said heating step isperformed at a temperature from about 50° C. to about 230° C.
 25. Amesoporous inorganic oxide spherical particle according to claim 1,wherein said heating step is performed at a temperature from about 70°C. to about 100° C.
 26. A mesoporous inorganic oxide spherical particleaccording to claim 1, wherein said heating step is performed for notmore than 60 minutes.
 27. A mesoporous inorganic oxide sphericalparticle according to claim 1, wherein said heating step producesmesostructured inorganic oxide spheres that are at least about 90%spherical.
 28. A mesoporous inorganic oxide spherical particle accordingto claim 1, wherein said removing step forms mesoporous inorganic oxidespherical particles having a pore volume of greater than about 0.65cm³/g.
 29. A mesoporous inorganic oxide spherical particle according toclaim 1, wherein said removing step forms mesoporous inorganic oxidespherical particles having a pore volume of greater than 0.75 cm³/g. 30.A plurality of mesoporous inorganic oxide spherical particles, eachcomprising one or more pores, wherein the spherical particles have apore volume of greater than 0.75 cm³/g and an average pore diameter ofgreater than 37 Angstroms.
 31. A plurality of mesoporous inorganic oxidespherical particles according to claim 30, wherein said pore volume isgreater than about 1 cm³/g and said average pore diameter is greaterthan about 50 Angstroms.
 32. A plurality of mesoporous inorganic oxidespherical particles according to claim 30, wherein said pore volume isgreater than about 1.3 cm³/g.